The main objective of this proposal is to improve the fidelity of fMRI localization to sites of neuronal activities. Two pre-requisites for achieving such an objective are uniform spatial coverage of relevant brain structures and accurate spatial localization of specific functional regions. Thus, we will develop improved acquisition methods that can ensure uniform spatial coverage in the presence of aggravated susceptibility artifacts at brain regions near air/tissue/bone interface and at high magnetic fields (e.g. 4T). We will also develop improved acquisition methods using dynamic apparent diffusion coefficient (ADC) contrast to achieve accurate spatial localization of the functional signal to the capillary networks that are closely tied to the neuronal activities. To this end, we propose three specific aims: First, improved acquisition methodology at high magnetic fields for uniform coverage and minimal distortion without the spatial confound of susceptibility artifacts will be developed and validated. Such method is especially needed at ventral brain regions where static susceptibility effects are pronounced. Second, improved acquisition methods with high temporal and spatial resolution will be developed to singularly detect synchronized ADC changes in capillary networks for close spatial coupling to the neuronal activities. Such signal changes will be compared with those obtained from the traditional blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) weighted contrasts to assess the improved spatial localization, using controlled visual activation paradigms. Third, using activated regions from the invasive intra-cranial electrical grid recordings during face and object recognition tasks as a standard, further validation of the localization ability of the susceptibility-compensated dynamic ADC contrast (optimized in the first two aims) in the ventral and middle temporal brain areas will be carried out using the same activation tasks. In parallel, the activated brain regions will also be used as seed points to initiate a diffusion tensor imaging (DTI) based nerve fiber tracking process to non-invasively validate their neuronal origins, based upon the knowledge that areas closely tied to the functioning neuronal populations are well connected by neural pathways. Together these three specific aims will help achieve the ultimate goal of neuroimaging for reliable, accurate and efficient localization of the neuronal activities, creating a comprehensive platform for assessing brain anatomy, function and neural pathways. It is anticipated that successful completion of the current research project will greatly improve the spatial specificity of the functional localization, effectively bridging the gap between neuroanatomy and neuroimaging.